T_regs produced by mesenchymal stromal cells with novel technique

A new study has suggested for the first time that regulatory T cells (T_regs) induced by mesenchymal stromal cells (MSCs) can produce an abundant replacement for naturally occurring T cells, vital in protecting the body from infection.

The researchers, at the Instituto de Medicina Molecular, Portugal, say their findings could lead to the development of new treatments for many chronic inflammatory diseases, including cancer, asthma, inflammatory bowel disease and rheumatoid arthritis. 

“T_regs play a critical role in immune tolerance,” said lead researcher Dr Rita Azevedo. “In stem cell transplantation to treat leukaemia and other blood diseases, for example, lower T_reg counts are associated with the development of chronic graft-versus-host disease. However, T_regs are very scarce. Finding alternative sources of stable T_reg induction might produce a large enough number for effective treatment uses.”

MSCs have previously been suggested as one way to achieve this. These are multipotent progenitor cells, which can be isolated from a wide range of adult and postnatal tissues and are able to differentiate into diverse cell types. Like T_regs, MSCs constitute an important immunoregulatory population by inhibiting both innate and adaptive immune responses.

“Thus far, the potential of MSC to recruit T_regs has been poorly understood,” Dr Azevedo said.

Previous studies have suggested that MSC-mediated immunomodulation may be partly driven by T_reg induction and/or expansion. However, these reports have not assessed T_reg yield in terms of absolute counts and have not characterised the resulting T_reg-like cells in detail. In the present study, Dr Azevedo’s team sought to determine whether MSCs are able to induce and/or expand T_reg in vitro, as well as the mechanisms of T_reg enrichment by MSC.

The researchers collected human peripheral blood mononuclear cells – including T cells – from healthy donors and co-cultured them with allogeneic bone marrow-derived MSCs. Fourteen days later, the results revealed an increase in the count and frequency of T_reg cells, at four- and six-fold, respectively.

According to the scientists, the MSC-induced T_reg-like cells resemble T_reg functionally and their DNA methylation profile closely resembles that of natural T_regs, indicating that this population is stable. 

“Our data sheds new light into the origin, functional potential and stability of MSC-induced T_reg-like cells, which are key features for their potential applicability in the clinical setting,” Dr Azevedo concluded. “The co-administration of MSCs and T_regs might have the potential to constitute a more effective cellular therapy approach by harnessing the suppressive capacity of both these immunomodulatory populations.”

The study was published in STEM CELLS.